Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000952448
Ethics application status
Approved
Date submitted
12/08/2025
Date registered
29/08/2025
Date last updated
29/08/2025
Date data sharing statement initially provided
29/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Enhancing memory and thinking in Mild Cognitive Impairment: An 18-week study using brain stimulation and cognitive training in older adults
Scientific title
An 18-week, randomised, double-blind, sham-controlled pilot study investigating the effects of computerised and strategy-based cognitive training combined with intermittent theta burst stimulation on memory and cognitive function in older adults with Mild Cognitive Impairment
Secondary ID [1] 314946 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
iCog.X Boost
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 338262 0
Condition category
Condition code
Neurological 334557 334557 0 0
Dementias
Mental Health 334558 334558 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Computerised Cognitive Training (CCT) + Intermittent Theta Burst Stimulation (iTBS):
Week 1 – Combined Delivery (In-Person):
Over 5 consecutive weekdays, participants attend in-person sessions at Western Sydney University (NICM or Campbelltown campus). Each daily session is approximately 3 hours in total, comprising:
iTBS: 5 sessions per day (10 minutes apart), targeting the left dorsolateral prefrontal cortex (DLPFC), for a total of 25 sessions (15,000 pulses).
• Delivered using MagPro X100 or MagStim Super Rapid2 Plus1 stimulators.
• Coil positioned with neuronavigation (Brainsight, BeamF3).
• Stimulation parameters: 3 pulses at 50 Hz, repeated at 5 Hz, delivered in 2-second trains with 8-second inter-train intervals, at 75% resting motor threshold (RMT), adjusted daily.
• Delivered by the chief investigator (an occupational therapist/neuroscientist with 1 year of intensive TMS training), under the ongoing supervision of a neuroscientist and TMS expert.
• Rest: 20-minute rest period following iTBS.
CCT (In-Person): 1-hour one-to-one session, delivered on a computer by the same occupational therapist (chief investigator) with extensive experience in cognitive training.
• Format: Computer-based interactive tasks; one-on-one delivery with real-time guidance.
• Example exercises from the iCog.X Boost program: visual memory grids, auditory memory tasks, divided attention dual-tasks, logical reasoning exercises, and problem-solving strategy exercises. These sessions focus on teaching participants cognitive strategies that will later be applied in the online training.
• Adherence monitoring: Daily attendance checklists for both iTBS and CCT are maintained by the research team.

Weeks 2–10 – CCT Only (Online):
Participants continue the CCT intervention independently online for an additional 9 weeks.
• Delivery: ~1 hour per week (9 sessions), via a secure, university-hosted platform (developed in Flask Python and hosted through pythonanywhere).
• Training Content: Same training modules as in-person, ensuring continuity. The online mode includes interactive activities, instructional videos, images, and practice questions. Unlike the in-person sessions, these modules are self-paced, with automated feedback and performance adaptation.
• Psychoeducation: Two small-group sessions (each ~2 hours: 90 minutes content + 30 minutes group discussion) are delivered via Zoom by a registered psychologist. These occur during the online training phase, specifically, one session in Week 5 and the second in Week 8 of the 10-week intervention period. Content includes videos, slides, interactive exercises, and collaborative discussion of cognitive strategies.
• Home-Based Tasks: Weekly assignments encourage transfer of skills into daily life. Examples include:
• Memory challenges (recall a shopping list or recipe ingredients without notes).
• Strategy-based activities (chunking information when learning new material).
• Reflection questions or short quizzes on strategy use.
• Adherence Monitoring: Online session completion is automatically logged by the platform. Attendance at psychoeducation sessions is recorded, and reminders/support are provided via phone and email.

Sham iTBS Condition:
Participants receive the same cognitive training protocol as the active intervention group. Sham stimulation is delivered using the same figure-of-eight coil rotated 180°, which substantially reduces magnetic field penetration while preserving the auditory and tactile sensations of active stimulation. Sham iTBS is administered over 5 consecutive days (3 pulses at 50 Hz, repeated at 5 Hz, delivered in 2-second trains with 8-second inter-train intervals, 5 sessions/day for 5 days, total 25 sessions). This method maintains blinding integrity and has been validated in previous TMS trials.
Intervention code [1] 331545 0
Treatment: Other
Intervention code [2] 331546 0
Rehabilitation
Intervention code [3] 331547 0
Behaviour
Comparator / control treatment
No Intervention (Waitlist Control Group)
Participants in this group receive no cognitive training or brain stimulation during the 10-week intervention period. They complete the same baseline, mid-point, and follow-up assessments as the intervention groups.
To ensure equitable access, participants in the waitlist control group will be offered the full CCT program after completing their final follow-up assessment. This occurs approximately 19 weeks after enrolment (i.e., following the completion of baseline, week 5, week 10, and 8-week post-intervention follow-up assessments).
Control group
Active

Outcomes
Primary outcome [1] 342233 0
Change in long delay free recall - verbal memory
Timepoint [1] 342233 0
Baseline (Week 0), Week 5 (mid-intervention), Week 10 (post-intervention, primary timepoint), Week 18 (8-week follow-up)
Secondary outcome [1] 450047 0
Change in attention span
Timepoint [1] 450047 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [2] 450048 0
Change in processing speed
Timepoint [2] 450048 0
Baseline (Week 0), Week 5, Week 10 (primary), Week 18
Secondary outcome [3] 450049 0
Change in reasoning ability
Timepoint [3] 450049 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [4] 450050 0
Change in everyday problem-solving
Timepoint [4] 450050 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [5] 450051 0
Change in functional independence (iADLs)
Timepoint [5] 450051 0
Baseline (Week 0), Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [6] 450052 0
Change in depressive symptoms
Timepoint [6] 450052 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [7] 450053 0
Change in anxiety symptoms
Timepoint [7] 450053 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [8] 450054 0
Change in sleep quality
Timepoint [8] 450054 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [9] 450055 0
Change in health-related quality of life
Timepoint [9] 450055 0
Baseline (Week 0), Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [10] 450056 0
Feasibility of the intervention
Timepoint [10] 450056 0
Post-intervention (after Week 18)
Secondary outcome [11] 450057 0
Change in cortical inhibition
Timepoint [11] 450057 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [12] 450058 0
Change in cortical activity – event-related potentials (ERPs) during Go/NoGo task
Timepoint [12] 450058 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up)
Secondary outcome [13] 451335 0
Acceptability of the intervention
Timepoint [13] 451335 0
Post-intervention (after Week 18).
Secondary outcome [14] 451336 0
Change in cortical activity – resting-state EEG (rsEEG)
Timepoint [14] 451336 0
Baseline (Week 0), Week 5, Week 10 (post-intervention), Week 18 (follow-up).
Secondary outcome [15] 451666 0
Change in working memory span
Timepoint [15] 451666 0
Baseline (Week 0), Week-5, Post-intervention (Week 10), Follow-up (Week 18)
Secondary outcome [16] 451667 0
Change in cortical excitabilityChange in cortical excitability
Timepoint [16] 451667 0
Paired-pulse TMS protocols, including short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI)

Eligibility
Key inclusion criteria
• Aged 55–85 years
• Clinical characterisation of Mild Cognitive Impairment (MCI) based on Winblad criteria, including:
• Subjective cognitive complaints via semi-structured clinical interview
• Objective cognitive decline:
• Memory Alteration Test (M@T) score greater than or equal to 37, OR
• Performance 1.0–1.5 standard deviations below age-adjusted norms and/or estimated premorbid ability (Test of Premorbid Functioning [ToPF])
• Preserved or minimal instrumental activities of daily living (iADL) impairment, based on HBA-FAQ and study neuropsychologist discretion
• Right-handed (Edinburgh Handedness Inventory)
• Fluent in English (reading, writing, speaking)
• Normal or corrected-to-normal vision and hearing
• Access to a personal desktop or laptop with full internet access
Minimum age
55 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Prior exposure to transcranial magnetic stimulation (TMS) within the past 12 months
• Memory Alteration Test (M@T) score 30 minutes, retrograde amnesia, post-traumatic concussion syndrome, or structural brain abnormalities

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation via REDCap’s randomisation module, with allocation sequence computer-generated by a university staff member external to the research team. The allocation sequence is inaccessible to study personnel involved in eligibility assessment or outcome measurement. Group assignment is revealed via REDCap only after baseline assessments, ensuring concealment until the point of allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated stratified block randomisation using REDCap’s randomisation module, with varying block sizes of 6 and 9. Stratification is by sex to ensure balanced allocation across the three study groups (CT + iTBS, CT + sham-iTBS, waitlist control).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
An a priori sample size calculation was conducted using G*Power 3.1, powered at 80 percent with alpha set at 0.05, assuming three groups (CCT plus iTBS, CCT plus sham-iTBS, waitlist), six repeated measures (Week 0, Week 1 [post-iTBS], Week 5, Week 10 [post-CCT], and Week 18 [8-week follow-up]), a moderate effect size (Cohen’s f of 0.18; Hedges’ g approximately 0.36 from Hill et al., 2017), and correlation among repeated measures of 0.5. This indicated a required total sample size of 52 to detect a group by time interaction. Allowing for 20 percent attrition (based on previous trials in this population), the target sample size is 66 (22 per group).

Primary and secondary outcomes will be analysed using linear mixed-effects models with fixed effects for group, time, and their interaction; participant ID as a random effect; and planned contrasts at the primary endpoint (Week 10). Model assumptions will be checked, and robust methods or transformations applied if violated. Multiple comparisons will be adjusted (for example, using the Holm method). Effect sizes and 95 percent confidence intervals will be reported.

Sensitivity analyses will adjust for age, sex, and education. Missing data will be addressed using multiple imputation under the Missing At Random (MAR) assumption. Intention-to-treat will be the primary analysis, with per-protocol analyses conducted as supportive. Exploratory correlations and regressions will examine relationships between neurophysiological changes (paired-pulse TMS, EEG) and cognitive outcomes. Analyses will be conducted in SPSS and/or R by a blinded analyst.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2025
Actual
Date of last participant enrolment
Anticipated
11/08/2026
Actual
Date of last data collection
Anticipated
15/12/2026
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 319501 0
Government body
Name [1] 319501 0
National Health and Medical Research Council (NHMRC) – Investigator Grant (Emerging Leadership 2) awarded to A/Prof Genevieve Z. Steiner-Lim
Country [1] 319501 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
Country
Australia
Secondary sponsor category [1] 321995 0
None
Name [1] 321995 0
Address [1] 321995 0
Country [1] 321995 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318077 0
University of Western Sydney Human Research Ethics Committee
Ethics committee address [1] 318077 0
Ethics committee country [1] 318077 0
Australia
Date submitted for ethics approval [1] 318077 0
30/01/2025
Approval date [1] 318077 0
07/05/2025
Ethics approval number [1] 318077 0
H16500

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 143042 0
A/Prof Genevieve Z. Steiner-Lim
Address 143042 0
NICM Health Research Institute, Western Sydney University, Westmead Innovation Quarter, 161 Hawkesbury Road, Westmead NSW 2145
Country 143042 0
Australia
Phone 143042 0
+61 0410342397
Fax 143042 0
Email 143042 0
[email protected]
Contact person for public queries
Name 143043 0
Rose Mery Bou Merhy
Address 143043 0
NICM Health Research Institute, Western Sydney University, Westmead Innovation Quarter, 161 Hawkesbury Road, Westmead NSW 2145
Country 143043 0
Australia
Phone 143043 0
+61 0404692783
Fax 143043 0
Email 143043 0
[email protected]
Contact person for scientific queries
Name 143044 0
Rose Mery Bou Merhy
Address 143044 0
NICM Health Research Institute, Western Sydney University, Westmead Innovation Quarter, 161 Hawkesbury Road, Westmead NSW 2145
Country 143044 0
Australia
Phone 143044 0
+61 0404692783
Fax 143044 0
Email 143044 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• De-identified individual participant data:
• Published results
• Primary outcome(s)
• Safety data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Studies testing whether findings can be repeated or confirmed
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
A finite period of: 15 years
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
Yes: Requests will be reviewed by the study team to ensure alignment with the study’s aims and data governance requirements, and only de-identified data will be provided.



What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Ethical approval    H16500 - Human Ethics Approval - May 2025.pdf
Informed consent form    Participant Information Sheet and Consent form - iCog.X Boost.pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.